On November 20, Professor Sun Jinpeng’s team from the School of Basic Medical Sciences, Shandong University / Peking University, in collaboration with Professor He Jufang from City University of Hong Kong, Professor Zhang Yong and Associate Professor Tie Lu from Peking University, Professor Du Yang from The Chinese University of Hong Kong, Shenzhen, and Tang Yi from Beijing Xuanwu Hospital, published an online research paper titled “Elucidating pathway-selective biased CCKBR agonism for Alzheimer’s disease treatment” in Cell. Starting from clinical questions, the study clarified the functions of different G protein signaling pathways downstream of CCKBR in the progression of Alzheimer’s disease (AD) through a combination of clinical sample detection and animal models. By resolving the molecular mechanism by which the endogenous agonist CCK8s activates different G proteins (Gs, Gq, Gi) of CCKBR, it revealed the molecular biological basis of CCKBR signal bias. Based on this, the team successfully designed a Gq-biased agonist 3r1 with therapeutic potential. Animal models and transcriptome analysis demonstrated that 3r1 can inhibit neural/synaptic damage and clear Aβ deposition through the CCKBR-Gq-PLCB4-ADAM10 signaling axis, providing a novel strategy for the precise treatment of AD.